Genetically modified cells are the most complex medicinal products and thus require a well-thought-out manufacturing and control strategy to meet regulatory expectations. Key aspects of these regulatory demands for manufacturing and control will be discussed in view of the numerous new developments in the regulatory field.

This presentation will discuss, maintaining product comparability in accordance with new EMA guidance, key considerations when setting up comparability studies for GM cells, common pitfalls when introducing changes during development, and case studies and strategies for typical changes.

Stability studies are supposed to follow the principles of ICH Q1 and Q5C, however translating this for cell-based products needs some lateral thinking.  This talk will discuss the principles, common issues and mistakes and offer some examples from the literature that might be incorporated into stability studies.

Lentiviral vectors have the ability to be pseudotyped with different glycoproteins. This work discusses the main challenges lentiviral vector manufacturing focusing on the use of alternative envelopes to VSV-G and how this strategy may impact bioprocess and vector quality evaluation namely in terms of cell transduction efficiency.

The business model for allogeneic cell therapies can appear similar to that of traditional biotech products, however with the exception of some stem cells, banked cells from a single donor are unlikely to last the whole product lifecycle. This means various aspects of banking will differ between products. This talk will consider some of these factors, their regulatory implications, and how to address them.

ATMPs characterization play important roles in providing CMC information for regulatory applications. Each type of ATMP presents different analytical development challenges. The presentation will show evolving validation requirements and analytical methods through the product’s life cycle, from early-stage development to commercial use and  case studies of analytical method development and validation in cell therapy through the product’s life cycle.

Manufacturing of cell and gene therapy products requires robust methods but also continuous improvement. The safety of the product, and the patient, must always be the major concern and depends upon our capacity to evolve our manufacturing methods without affecting the potency of the product. The presentation will show Cellectis strategy to refine our UCART manufacturing towards a science-based industrial method.

This presentation will discuss, establishing a process control strategy facilitates process intensification, increasing yield and efficiency, automated strategies for process and product development enable increased consistency. Improved control allows for the potential of patient-specific adaptive manufacturing.

Analysis of high concentration protein formulations poses some challenges. Molecular crowding and dipolar interactions lead to self-association with increased viscosity and changes in fluid dynamics. Sub-visible particles (SVPs) pose a major challenge in the development of high concentration protein formulations. Distinction between proteinaceous and other SVPs is vital in monitoring form stability. The current LO method has limitations to detect translucent particles. Thus, an unambiguous method to characterize SVPs is needed. This talk will discuss some of the techniques to characterize and distinguish SVPs in protein formulations by MFI/FlowCam/SLIM with the MIA and Lumetics.

With emerging non-mabs like Fc silencing formats, bispecific mabs, therapeutics proteins, and newer modalities such as gene therapies and AAV’s, designing stable liquid formulation is more challenging. Co-development of the clinical service formulation enables an in-depth understanding of the degradation pathways and the possibility of a stable liquid formulation. With the use of forced degradation studies and high throughput biophysical predictive tools, key developability questions can be addressed.

Adenovirus vectors offer a versatile vaccine platform. The Oxford Jenner Institute ChAdOx platform is licensed for Ebola and the Oxford-AstraZeneca COVID-19 vaccine which has been administered to >500m people. Distribution and storage at 2-8 °C is possible for months, but storage at higher temperatures would enable easier access to communities and people in regions without cold-chains. Here we present the formulation and process development for stable freeze-dried ChAdOx vaccines.

There is significant need to improve existing AAV manufacturing platforms to achieve robust, high-yielding, scalable, and cost-efficient processes. At Ultragenyx we employ scalable AAV production processes using mammalian producer cell lines that eliminate the high cost of goods associated with the traditional AAV platforms. In the following presentation, we demonstrate how we have improved on our existing platform process through process intensification to achieve a several-fold increase in overall volumetric AAV yield. Through process intensification, we have increased our AAV platforms productivity to =3E11 GC/mL (=3 E14 GC/L).

With the first products now to market, mRNA represents a disruptive technology with broad applications and the potential for a platform manufacturing approach. This talk will outline our experiences evaluating and developing a modular manufacturing platform for mRNA, and view to how such processes could be intensified.